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Background The efficacy of anti-PD-1 therapy is primarily hindered by the limited T-cell immune response rate and immune evasion capacity of tumor cells. Autophagy-related protein 7 (ATG7) plays an important role in autophagy and it has been linked to cancer. However, the role of ATG7 in the effect of immune checkpoint blockade (ICB) treatment on high microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR) CRC is still poorly understood. Methods In this study, patients from the cancer genome altas (TCGA) COAD/READ cohorts were used to investigate the biological mechanism driving ATG7 development. Several assays were conducted including the colony formation, cell viability, qRT-PCR, western blot, immunofluorescence, flow cytometry, ELISA, immunohistochemistry staining and in vivo tumorigenicity tests. Results We found that ATG7 plays a crucial role in MSI-H CRC. Its knockdown decreased tumor growth and caused an infiltration of CD8 + T effector cells in vivo. ATG7 inhibition restored surface major histocompatibility complex I (MHC-I) levels, causing improved antigen presentation and anti-tumor T cell response by activating reactive oxygen species (ROS)/NF-κB pathway. Meanwhile, ATG7 inhibition also suppressed cholesterol accumulation and augmentation of anti-tumor immune responses. Combining ATG7 inhibition and statins improved the therapeutic benefit of anti-PD-1 in MSI-H CRC. Importantly, CRC patients with high expression of both ATG7 and recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) experienced worse prognosis compared to those with low ATG7 and HMGCR expression. Conclusions Inhibition of ATG7 leads to upregulation of MHC-I expression, augments immune response and suppresses cholesterol accumulation. These findings demonstrate that ATG7 inhibition has therapeutic potential and application of statins can increase the sensitivity to immune checkpoint inhibitors.

Fluorouracil-based chemotherapy responses in colorectal cancer (CRC) patients vary widely, highlighting the role of pharmacogenomics in developing better predictive models. We analyzed 379 CRC patients receiving fluorouracil-based chemotherapy, collecting data on fluorouracil metabolism-related SNPs ( TYMS , MTHFR , DPYD , RRM1 ), blood inflammatory markers, and clinical status. Six machine learning models—K-nearest neighbors, support vector machine, gradient boosting decision trees (GBDT), eXtreme Gradient Boosting (XGBoost), LightGBM, and random forest—were compared against multivariate logistic regression and a deep learning model (i.e., multilayer perceptron, MLP). Feature importance analysis highlighted seven predictors: histological grade, N and M staging, monocyte count, platelet-to-lymphocyte ratio, MTHFR rs1801131, and RRM1 rs11030918. In a five-fold cross-validation, XGBoost and GBDT exhibited superior performance, with Area Under Curve (AUC) of 0.88 ± 0.02. XGBoost excelled in identifying favorable prognosis (recall = 0.939). GBDT demonstrated balance in recognizing both categories, with a recall for favorable prognosis of 0.908 and a precision for unfavorable prognosis of 0.863. MLP had a similar AUC (0.87) with high precision for favorable prognosis (recall = 0.946). In external validation, XGBoost model achieved an accuracy of 0.79. An online prognostic tool based on XGBoost was developed, integrating metabolism-related SNPs and inflammatory markers, enhancing CRC treatment precision and supporting tailored chemotherapy.

Serum liver enzymes are frequently tested in clinics to aid disease diagnosis. Large observational studies indicated that these enzymes might predict cancer risk and mortality. However, no prospective study has reported on their relationships with the risk of HBV-related hepatocellular carcinoma (HCC). We evaluated the predictive values of four routinely tested liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT]) in HCC risk in a prospectively enrolled clinical cohort of 588 Korean American HBV patients. For all four enzymes, the baseline level as well as the average and maximum levels during the first 1 or 2 years of follow-up were analyzed using multivariate Cox proportional hazards model. Patients were categorized into a normal or an elevated group based on the clinical cut-off of each enzyme. During a median follow-up of 7.5 years, 52 patients (incidence rate, 8.8%) developed HCC. The incidence rates were higher in the elevated groups for all four enzymes. The most significant finding was for GGT, with the highest incidence rate of 16.4% in the elevated group compared to 4.6% in the normal group (P<0.001). Compared to patients with normal baseline GGT, those with elevated GGT exhibited a significantly increased HCC risk with a hazards ratio (HR) of 2.60 (95% confidence interval [CI], 1.41-4.77, P = 0.002). Further analyses revealed a cumulative effect between baseline GGT and ALP (HR = 3.41, 95% CI 1.54-7.56, P = 0.003). Serum GGT might predict HCC risk in HBV patients individually or jointly with other enzymes.

Purpose To study the correlations of genetic variants of telbivudine phosphorylase kinases and telbivudine plasma concentration with creatine kinase elevation in chronic hepatitis B patients who received telbivudine. Methods An observational study was performed in China chronic hepatitis B patients receiving telbivudine therapy at 600 mg once daily. Plasma concentration was measured 12 h after taking telbivudine using ultra-performance liquid chromatography–tandem mass spectrometry and SNPs located in RRM2B , TK2 , and NME4 was detected by MALDI-TOF mass spectrometry. All statistical analyses were performed with R 4.3.1 and all graphs were drawn by Origin 2023b and P value < 0.05 was considered statistically significant. Results A total of 140 patients receiving telbivudine therapy were recruited with a median plasma concentration of 952.49 (781.07–1238.98) ng/mL. The value of plasma concentration was proportional to the grade of creatine kinase elevation and the best telbivudine plasma concentration threshold to discriminate the grade 3/4 CK elevation was 1336.61 ng/mL. Multivariate analysis revealed that plasma concentration and rs3826160 were the independent risk factor of telbivudine-induced creatine kinase elevation. Patients with TC and CC genotype in rs3826160 not only had a higher incidence of creatine kinase elevation but also a higher plasma concentration than TT genotype carriers. Conclusion Chronic hepatitis B patients with TC and CC genotype in rs3826160 have high telbivudine plasma concentration are at risk of elevated creatine kinase.

Purpose An increasing number of studies are reporting a high frequency of creatine kinase (CK) elevation during telbivudine therapy; however, few reports have focused on the cumulative incidence and risk factors of CK elevation. This study was performed to investigate the cumulative incidence and risk factors of CK elevation in Chinese patients treated with telbivudine. Methods In this observational study, patients with chronic hepatitis B receiving telbivudine therapy between July 2008 and December 2013 were enrolled. The cumulative incidence of CK elevation was analyzed using the Kaplan–Meier method combined with the log rank test. Risk factors were determined using Cox proportional hazards regression models. Results A total of 207 eligible patients were analyzed. The cumulative incidence of CK elevation at 12, 24, 36, 48, 60, and 72 months was 51.2 %, 68.9 %, 75.1 %, 78.1 %, 78.1 %, and 78.1 %, respectively. Multivariate analysis revealed that male and lower baseline estimated glomerular filtration rate (eGFR) were significant risk factors for CK elevation. Conclusions The cumulative incidence of CK elevation after long-term telbivudine use is quite high, and gender and baseline eGFR may be useful predictors. However, when combined with regular monitoring of CK levels, especially for patients with lower eGFR, telbivudine is a relatively safe nucleoside analog treatment for chronic hepatitis B.

Telbivudine (LdT) is an antiviral agent currently used in the treatment of chronic hepatitis B virus, which was first approved by the US FDA in 2006. The safety of LdT is of great importance for patients that receive long-term treatment for this condition. It has been confirmed that patients treated with LdT have significantly elevated creatine kinase levels. However, the mechanism responsible for this adverse reaction is unclear. This review summarizes the current literature of the adverse reactions of LdT and the possible mechanisms that are involved in chronic hepatitis B infection. Thus, we aim to provide guidance on best practices in using LdT and to provide evidence of the possible mechanisms of LdT-associated adverse reactions.

Background Streptococcus salivarius is an opportunistic pathogen, and there have been no reported cases of Streptococcus salivarius pneumonia to date. Pneumomediastinum is usually secondary to tracheal or esophageal injury and is very rare as a complication of pneumonia. We report a case of Streptococcus salivarius pneumonia complicated by pneumomediastinum, aiming to enhance clinicians’ awareness of rare pathogens and uncommon complications in pneumonia. Case presentation The patient, a 36-year-old male, presented with a persistent cough and sputum production for one week, accompanied by a sore throat that had developed just one day prior. Chest computed tomography (CT) disclosed pneumomediastinum alongside obstructive atelectasis in the left lower lobe. Streptococcus salivarius infection was conclusively identified through bronchoalveolar lavage metagenomic next-generation sequencing (mNGS), as well as smear and culture analyses. The patient was administered intravenous amoxicillin-clavulanate potassium for a duration of seven days as part of the anti-infection regimen. Given the stability of the patient’s respiratory and circulatory systems, a tube drainage procedure was deemed unnecessary. Post-treatment, the patient’s clinical symptoms notably improved. A subsequent chest CT scan revealed the re-expansion of the left lower lung and near-complete resolution of pneumomediastinum. Conclusion There are numerous pathogens that can cause pneumonia. While focusing on common pathogens, it is important not to overlook rare ones. When considering infections from rare pathogens, it is recommended to promptly perform a bronchoscopy and submit bronchoalveolar lavage fluid for mNGS to improve pathogen detection rates. During the diagnosis and treatment of pneumonia, it is crucial to be vigilant for rare complications. When a patient presents with symptoms such as dyspnea or subcutaneous emphysema, it is advisable to immediately perform a chest CT scan to rule out pneumomediastinum.